PMID- 21497593
OWN - NLM
STAT- MEDLINE
DCOM- 20110906
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 660
IP  - 2-3
DP  - 2011 Jun 25
TI  - Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on 
      extracellular dopamine and serotonin in the rat brain.
PG  - 318-25
LID - 10.1016/j.ejphar.2011.03.050 [doi]
AB  - 3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive stimulant abused by 
      young people as the recreational drug ecstasy. Other compounds, either 
      deliberately added or present as byproducts, are often found in MDMA tablets and 
      can unexpectedly interact with each other. The aim of this study was to evaluate 
      the pharmacodynamic effects of interactions caused by concomitants in MDMA 
      tablets on extracellular dopamine and serotonin (5-HT) by microdialysis in the 
      striatum of ethylcarbamate-anesthetized rats. Baseline levels of dopamine and 
      5-HT in the striatum were 16.5+/-7.7 and 3.5+/-1.7 nM (mean+/-standard deviation), 
      respectively. After a single administration of MDMA (10 mg/kg, i.p.), a dramatic 
      increase in extracellular dopamine (Cmax: 36.1-fold vs. baseline) and 5-HT levels 
      (Cmax: 9.3-fold vs. baseline) was observed. When rats were co-administered with 
      methamphetamine (1, 5 or 10 mg/kg) with MDMA, the dopamine levels induced by MDMA 
      increased in a methamphetamine-dose-dependent manner (Cmax: 2.5-, 3.5-, and 
      3.8-fold vs. MDMA). A similar trend was observed in 5-HT levels (Cmax: 1.1-, 
      1.3-, and 1.8-fold vs. MDMA). In contrast, ketamine and caffeine showed 
      synergistic effects on the monoamine levels induced by MDMA, whereas the 
      individual administration of either of these compounds did not affect monoamine 
      levels. Ketamine (1, 5 mg/kg) decreased the dopamine levels induced by MDMA 
      (Cmax: 0.9- and 0.7-fold vs. MDMA) and increased the 5-HT levels induced by MDMA 
      (Cmax: 1.4- and 1.6-fold vs. MDMA), and co-administration of caffeine (20 mg/kg) 
      with MDMA increased dopamine levels (Cmax: 1.7-fold vs. MDMA). These results 
      suggest that exposure to multiple drugs in addition to MDMA can have neurotoxic 
      effects.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Ikeda, Rie
AU  - Ikeda R
AD  - Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, 
      Nagasaki 852-8521, Japan.
FAU - Igari, Yoshiko
AU  - Igari Y
FAU - Fuchigami, Yuki
AU  - Fuchigami Y
FAU - Wada, Mitsuhiro
AU  - Wada M
FAU - Kuroda, Naotaka
AU  - Kuroda N
FAU - Nakashima, Kenichiro
AU  - Nakashima K
LA  - eng
PT  - Journal Article
DEP - 20110409
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Tablets)
RN  - 333DO1RDJY (Serotonin)
RN  - 3G6A5W338E (Caffeine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 690G0D6V8H (Ketamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Brain/*cytology/drug effects/metabolism
MH  - Caffeine/administration & dosage/pharmacology
MH  - Dopamine/*metabolism
MH  - Drug Interactions
MH  - Extracellular Space/*drug effects/*metabolism
MH  - Ketamine/administration & dosage/pharmacology
MH  - Male
MH  - Methamphetamine/administration & dosage/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*metabolism
MH  - Tablets
EDAT- 2011/04/19 06:00
MHDA- 2011/09/07 06:00
CRDT- 2011/04/19 06:00
PHST- 2010/07/10 00:00 [received]
PHST- 2011/03/07 00:00 [revised]
PHST- 2011/03/28 00:00 [accepted]
PHST- 2011/04/19 06:00 [entrez]
PHST- 2011/04/19 06:00 [pubmed]
PHST- 2011/09/07 06:00 [medline]
AID - S0014-2999(11)00367-0 [pii]
AID - 10.1016/j.ejphar.2011.03.050 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2011 Jun 25;660(2-3):318-25. doi: 10.1016/j.ejphar.2011.03.050. 
      Epub 2011 Apr 9.